1. Field of the Invention
The present invention relates to a group of bioinformatically detectable novel oligonucleotides, here identified as Genomic Address Messenger or GAM oligonucleotides, which are believed to be related to the micro RNA (miRNA) group of oligonucleotides.
2. Description of Prior Art
Micro RNAs (miRNA), are short ˜22 nt non-coding regulatory RNA oligonucleotides, found in a wide range of species, believed to function as specific gene translation repressors, sometimes involved in cell-differentiation.
The ability to detect novel miRNAs is limited by the methodologies used to detect such oligonucleotides. All miRNAs identified so far either present a visibly discernable whole body phenotype, as do Lin-4 and Let-7 (Wightman, B., Ha, I., and Ruvkun, G., Cell 75:855-862 (1993); Reinhart et al. Nature 403: 901-906 (2000)), or produce sufficient quantities of RNA so as to be detected by the standard molecular biological techniques.
Studies reporting miRNAs (Lau et al., Science 294:858-862 (2001), Lagos-Quintana et al., Science 294: 853-858 (2001)) discovered 93 miRNAs in several species, by sequencing a limited number of clones (300 by Lau and 100 by Lagos-Quintana) of small segments (i.e. size fractionated) RNA. MiRNAs detected in these studies therefore, represent the more prevalent among the miRNA oligonucleotide family, and can not be much rarer than 1% of all small ˜20 nt-long RNA oligonucleotides.
The aforesaid studies provide no basis for detection of miRNA oligonucleotides which either do not present a visually discernable whole body phenotype, or are rare (e.g. rarer than 0.1% of all size fractionated ˜20 nt-long RNA segments expressed in the tissues examined), and therefore do not produce significant enough quantities of RNA so as to be detected by standard biological techniques.
Previous studies on miRNAs and their relation to diseases have suggested potential involvement of several miRNAs in various type of cancers; It has been suggested that mir-15 and mir-16 are associated with B-cell chronic lymphocytic leukemia (Calin, G. A at al., Proc. Natl. Acad. Sci. U.S.A., 2002). More recently, researchers have shown strong evidence for involvement of mir-143 and mir-145 in colorectal neoplasia (Michael, M. Z. et al., Mol. Cancer Res. 1: 882-891 (2003)). Mietzler and colleagues have demonstrated that mir-155, which is located on BIC locus, is highly and differentially expressed in pediatric Burkit lymphoma patients (Metzler, M. at al. Cancer 39: 167-169 (2004)). Involvement of miRNAs in Alzheimers disease is unknown.
The following U.S. patents relate to bioinformatic detection of genes: U.S. Pat. No. 6,369,195, entitled “Prostate-specific gene for diagnosis, prognosis and management of prostate cancer”, and U.S. Pat. No. 6,291,666 entitled “Spike tissue-specific promoter”, each of which is hereby incorporated by reference herein.